Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: BCAP31

Gene summary for BCAP31

Gene summary.

Gene information	Species	Human
	Gene symbol	BCAP31
	Gene ID	10134
	Gene name	B cell receptor associated protein 31
	Gene Alias	6C6-AG
	Cytomap	Xq28
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P51572

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
10134	BCAP31	GSM4909282	Human	Breast	IDC	2.29e-30	6.44e-01	-0.0288
10134	BCAP31	GSM4909287	Human	Breast	IDC	3.78e-11	3.93e-01	0.2057
10134	BCAP31	GSM4909296	Human	Breast	IDC	3.47e-08	6.66e-03	0.1524
10134	BCAP31	GSM4909297	Human	Breast	IDC	1.98e-08	-1.20e-01	0.1517
10134	BCAP31	GSM4909304	Human	Breast	IDC	3.27e-08	3.77e-01	0.1636
10134	BCAP31	GSM4909306	Human	Breast	IDC	4.39e-07	3.51e-01	0.1564
10134	BCAP31	GSM4909309	Human	Breast	IDC	2.12e-02	1.77e-01	0.0483
10134	BCAP31	GSM4909311	Human	Breast	IDC	4.13e-29	-2.57e-01	0.1534
10134	BCAP31	GSM4909312	Human	Breast	IDC	2.65e-10	-6.27e-02	0.1552
10134	BCAP31	GSM4909317	Human	Breast	IDC	1.46e-10	4.37e-01	0.1355
10134	BCAP31	GSM4909319	Human	Breast	IDC	4.01e-43	6.07e-02	0.1563
10134	BCAP31	GSM4909320	Human	Breast	IDC	1.70e-05	-7.37e-02	0.1575
10134	BCAP31	GSM4909321	Human	Breast	IDC	2.39e-15	9.88e-02	0.1559
10134	BCAP31	brca1	Human	Breast	Precancer	5.39e-19	5.23e-01	-0.0338
10134	BCAP31	brca2	Human	Breast	Precancer	5.00e-14	3.91e-01	-0.024
10134	BCAP31	brca3	Human	Breast	Precancer	3.85e-08	2.73e-01	-0.0263
10134	BCAP31	NCCBC14	Human	Breast	DCIS	2.92e-14	-2.26e-01	0.2021
10134	BCAP31	NCCBC2	Human	Breast	DCIS	1.03e-04	8.73e-02	0.1554
10134	BCAP31	NCCBC5	Human	Breast	DCIS	8.11e-21	-1.35e-01	0.2046
10134	BCAP31	P1	Human	Breast	IDC	3.46e-22	-2.99e-01	0.1527

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:003497614	Breast	IDC	response to endoplasmic reticulum stress	43/1434	256/18723	8.42e-07	3.82e-05	43
GO:006113614	Breast	IDC	regulation of proteasomal protein catabolic process	33/1434	187/18723	5.24e-06	1.75e-04	33
GO:190336414	Breast	IDC	positive regulation of cellular protein catabolic process	29/1434	155/18723	5.93e-06	1.90e-04	29
GO:200005814	Breast	IDC	regulation of ubiquitin-dependent protein catabolic process	30/1434	164/18723	6.62e-06	2.05e-04	30
GO:007097213	Breast	IDC	protein localization to endoplasmic reticulum	18/1434	74/18723	8.58e-06	2.47e-04	18
GO:004316114	Breast	IDC	proteasome-mediated ubiquitin-dependent protein catabolic process	57/1434	412/18723	9.55e-06	2.68e-04	57
GO:190589714	Breast	IDC	regulation of response to endoplasmic reticulum stress	19/1434	82/18723	1.04e-05	2.87e-04	19
GO:004573214	Breast	IDC	positive regulation of protein catabolic process	37/1434	231/18723	1.46e-05	3.71e-04	37
GO:190305213	Breast	IDC	positive regulation of proteolysis involved in cellular protein catabolic process	25/1434	133/18723	2.34e-05	5.59e-04	25
GO:190180014	Breast	IDC	positive regulation of proteasomal protein catabolic process	22/1434	114/18723	4.68e-05	1.04e-03	22
GO:190495113	Breast	IDC	positive regulation of establishment of protein localization	45/1434	319/18723	5.01e-05	1.09e-03	45
GO:007058513	Breast	IDC	protein localization to mitochondrion	23/1434	125/18723	6.92e-05	1.40e-03	23
GO:000989614	Breast	IDC	positive regulation of catabolic process	62/1434	492/18723	7.06e-05	1.42e-03	62
GO:003243414	Breast	IDC	regulation of proteasomal ubiquitin-dependent protein catabolic process	24/1434	134/18723	7.59e-05	1.50e-03	24
GO:007265513	Breast	IDC	establishment of protein localization to mitochondrion	22/1434	120/18723	1.04e-04	1.97e-03	22
GO:00324368	Breast	IDC	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	18/1434	90/18723	1.39e-04	2.48e-03	18
GO:000660514	Breast	IDC	protein targeting	43/1434	314/18723	1.44e-04	2.53e-03	43
GO:20000609	Breast	IDC	positive regulation of ubiquitin-dependent protein catabolic process	20/1434	107/18723	1.61e-04	2.76e-03	20
GO:003133114	Breast	IDC	positive regulation of cellular catabolic process	54/1434	427/18723	1.85e-04	3.07e-03	54
GO:003246913	Breast	IDC	endoplasmic reticulum calcium ion homeostasis	8/1434	25/18723	3.85e-04	5.40e-03	8

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414118	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0414119	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414134	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414143	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0414153	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041412	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041413	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041415	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041416	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa041417	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa0414126	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa04141111	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa0414127	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa0414136	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa0414139	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa04141114	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

BCAP31

SNV

Missense_Mutation

c.851A>T

p.Glu284Val

p.E284V

P51572

protein_coding

deleterious(0)

probably_damaging(0.959)

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

BCAP31

SNV

Missense_Mutation

novel

c.572N>T

p.Ser191Leu

p.S191L

P51572

protein_coding

deleterious(0.02)

probably_damaging(0.991)

TCGA-AO-A03P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

BCAP31

SNV

Missense_Mutation

c.833N>T

p.Ala278Val

p.A278V

P51572

protein_coding

deleterious(0.05)

probably_damaging(0.997)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BCAP31

SNV

Missense_Mutation

rs782366321

c.554N>A

p.Arg185His

p.R185H

P51572

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

BCAP31

SNV

Missense_Mutation

novel

c.364N>T

p.Leu122Phe

p.L122F

P51572

protein_coding

tolerated(0.22)

benign(0.248)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BCAP31

SNV

Missense_Mutation

rs782016039

c.871N>A

p.Asp291Asn

p.D291N

P51572

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BCAP31

SNV

Missense_Mutation

novel

c.937N>A

p.Glu313Lys

p.E313K

P51572

protein_coding

deleterious(0.04)

benign(0.023)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

BCAP31

SNV

Missense_Mutation

c.421G>A

p.Asp141Asn

p.D141N

P51572

protein_coding

tolerated(0.16)

possibly_damaging(0.76)

TCGA-C5-A2LX-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BCAP31

SNV

Missense_Mutation

novel

c.850G>A

p.Glu284Lys

p.E284K

P51572

protein_coding

tolerated(0.1)

benign(0.233)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

BCAP31

SNV

Missense_Mutation

c.130N>A

p.Val44Met

p.V44M

P51572

protein_coding

tolerated_low_confidence(0.34)

benign(0)

TCGA-CM-6680-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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